Neurothrophins are crucial in the regulation of many processes, such as nerve cells development and neuroplasticity and brain-derived neurothrophic factor (BDNF) is the major one. Researchers still scrutinize the role of BDNF Val66Met polymorphism in eating disorders and cognition, however, literature present inconsistent findings regarding this topic. Most of all, the exact mechanism of how exactly BDNF influences cognitive functioning in obesity is unknown. In our study, we try to elucidate the association of BDNF Val66Met polymorphism with executive functions and working memory on large obese population. 375 obese patients underwent biometric analyses and neuropsychological assessment. The Wisconsin Card Sorting Test (WCST) was used to assess cognitive functions. Genetic polymorphism in BDNF was evaluated in peripheral blood samples.Results indicated that both BDNF Val66Met polymorphism and gender showed significant correlations with BMI, WCST_P and WCST_CLR. Females showed higher BMI values than men,, however males scored higher in WSCT_P and WSCT_CLR. Val/Val carriers presented worse results of WCST and BMI. Kendall's partial rank correlation tests determined that both genotype and BMI showed significant correlations with WCST_CLR, WCST_CC and WCST_1st, in which BMI correlation was stronger. Analysis of mild and morbid obesity showed, that severe obese younger subjects presented worse WCST_P, WCST_NP, and WCST_CLR. Significant interaction effects for WCST parameters were found for gender, age, BMI and BDNF Val66Met. Importantly, in this study none Met/Met carriers were observed.The Val66Met BDNF polymorphism indirectly influenced the poorer cognitive functioning observed in the obese subpopulation with Val/Val genotype, rather than Val/Met genotype. A higher BMI was associated with the Val allele, suggesting that obesity may have deteriorated the activity of the prefrontal cortex. According to results, BDNF Val66Met polymorphism seems to contribute to greater obesity in our study. It is greater BMI, rather than genotype, which caused worse executive functioning and working memory. KeywordsVal66Met BDNF, Neurothrophins, Obesity Neuropsychiatry (London) (2018) 8(1) 112Research Maciej Bieliński the worse scores in WCST, and how BDNF Val66Met influences the severity of obesity. Materials and Methods ParticipantsA total of 375 adult Caucasian patients of Polish nationality were enrolled in this study, including 233 women and 142 men, after excluding secondary reasons of obesity. The mean age of all participants was 54 (range, 20-76) years old; the mean age for women was 52 (20-75) years old, and for men 56 (42-67) years old. The exclusion criteria were individuals with a severe somatic or psychiatric disorder included in the Diagnostic